Publications by authors named "Rosa Faner"

80 Publications

Lung function trajectory and biomarkers in the Tasmanian Longitudinal Health Study.

ERJ Open Res 2021 Jul 13;7(3). Epub 2021 Sep 13.

Allergy and Lung Health Unit, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.

Background And Objective: Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories.

Methods: The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories.

Results: Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63-0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00-1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56-0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53-0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60-0.83, p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (interleukin (IL)-4, IL-5, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)) were not significantly different between AD, ND and controls.

Conclusions: Circulating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (AD ND) leading to COPD at age 53 years.
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http://dx.doi.org/10.1183/23120541.00020-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435806PMC
July 2021

Cellular Senescence in Lung Fibrosis.

Int J Mol Sci 2021 Jun 29;22(13). Epub 2021 Jun 29.

Department of Pulmonology, ICR, Hospital Clinic, 08036 Barcelona, Spain.

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.
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http://dx.doi.org/10.3390/ijms22137012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267738PMC
June 2021

Spirometry: A practical lifespan predictor of global health and chronic respiratory and non-respiratory diseases.

Eur J Intern Med 2021 07 18;89:3-9. Epub 2021 May 18.

Respiratory Medicine, University of Ferrara; Emergency Department, University Hospital S. Anna, Ferrara, Italy.

Objectives: 1. To review and discuss available evidence supporting that spirometry is an overlooked global health marker, that could be used regularly through the lifespan to monitor human health and predict risk of chronic respiratory and other chronic non-communicable diseases (NCDs). 2. To discuss the challenges and opportunities that this proposal faces.Summary of key data. First, spirometry is essential to assess and monitor respiratory health. Second, spirometry adds prognostic value to other well-accepted health markers used in clinical practice, such as blood pressure, body mass index, glucose and blood lipids, by identifying individuals at risk, not only of respiratory diseases, but also of other NCDs, particularly cardiovascular and metabolic disorders.

Conclusion: Although we acknowledge that research gaps still exist, we propose that spirometry assessed during childhood, adolescence and early and late adulthood can be a reproducible, non-invasive, safe and affordable global health marker to identify individuals in the general population at risk of respiratory and non-respiratory NCDs. In this context, spirometry may act as the caged canaries that miners used to carry into mines to alert them of dangerous accumulations of gases, thus providing an early warning and save lives.
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http://dx.doi.org/10.1016/j.ejim.2021.04.027DOI Listing
July 2021

Chronic bronchial infection and incident cardiovascular events in chronic obstructive pulmonary disease patients: A long-term observational study.

Respirology 2021 08 18;26(8):776-785. Epub 2021 May 18.

Centro de Investigación Biomédica en Red (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.

Background And Objective: Cardiovascular (CV) diseases are frequent in patients with chronic obstructive pulmonary disease (COPD). Likewise, chronic bronchial infection (CBI) is also frequent in COPD and it is associated with systemic inflammation, a well-known CV risk factor. The objective of this study was to investigate the relationship between CBI, systemic inflammation and incident CV events.

Methods: A post hoc analysis of prospectively collected cohort of 201 COPD patients [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] followed up every 3-6 months for 84 months was conducted. CBI was defined as ≥3 positive pathogenic microorganisms sputum cultures over 1 year, separated by ≥3 months. Systemic inflammation was assessed by circulating levels of C-reactive protein and fibrinogen. Fatal and non-fatal CV events, including coronary and cerebrovascular events as well as arrhythmia episodes, were prospectively recorded. For analysis, they were analysed separately and combined in a composite variable.

Results: As hypothesized, CBI was associated with persistent systemic inflammation and a significantly higher incidence of CV events (HR: 3.88; 95% CI: 1.83-8.22), mainly of coronary origin independent of age, number and severity of exacerbations, comorbidities, other CV risk factors, lung function, BMI, smoking status and treatments. These associations were particularly significant in patients with CBI by Pseudomonas aeruginosa (PA).

Conclusion: CBI, particularly by PA, is associated with sustained and enhanced systemic inflammation and a higher incidence of CV events (especially coronary events). The possibility that treating CBI may decrease systemic inflammation and CV events in COPD deserves prospective, interventional studies.
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http://dx.doi.org/10.1111/resp.14086DOI Listing
August 2021

Molecular Interactions of SARS-CoV-2 in Lung Tissue of Patients with Chronic Obstructive Pulmonary Disease.

Ann Am Thorac Soc 2021 May 5. Epub 2021 May 5.

Institut d'Investigacions Biomèdiques August Pi i Sunyer, 146245, Barcelona, Catalunya, Spain;

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http://dx.doi.org/10.1513/AnnalsATS.202006-619RLDOI Listing
May 2021

Risk Factors and Relation with Mortality of a New Acquisition and Persistence of in COPD Patients.

COPD 2021 06 3;18(3):333-340. Epub 2021 May 3.

Centro de Investigación Biomedica en Red (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.

The isolation of (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased mortality. Yet, factors associated with first PA sputum isolation, and PA persistence have not been investigated before. The objective of the present study was to investigate risk factors for new acquisition and persistence of PA infection and their relationship with all-cause mortality in patients with COPD. analysis of prospectively collected cohort of 170 COPD patients (GOLD II-IV) who were free of previous PA isolation and followed up every 3-6 months for 85 [50.25-110.25] months. PA was isolated for the first time in 41 patients (24.1%) after 36 [12-60] months of follow-up. Risk factor for first PA isolation were high cumulative smoking exposure, severe airflow limitation, previous severe exacerbations, high fibrinogen levels and previous isolation of PA was isolated again one or more times during follow-up in 58.5% of these patients. This was significantly associated with the presence of CT bronchiectasis and persistence of severe exacerbations, whereas the use of inhaled antibiotic treatment after the first PA isolation (at the discretion of the attending physician) reduced PA persistence. During follow-up, 79 patients (46.4%) died. A single PA isolation did not increase mortality, but PA persistence did (HR 3.06 [1.8-5.2],  = 0.001). We conclude that PA occurs frequently in clinically stable COPD patients, risk factors for a first PA isolation and PA persistence are different, and the latter (but not the former) is associated with increased all-cause mortality.
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http://dx.doi.org/10.1080/15412555.2021.1884214DOI Listing
June 2021

Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19.

Lancet Respir Med 2021 07 9;9(7):682-683. Epub 2021 Apr 9.

Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; CIBER Enfermedades Respiratorias, Spain.

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http://dx.doi.org/10.1016/S2213-2600(21)00171-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040539PMC
July 2021

Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.

Respir Res 2021 Apr 6;22(1):100. Epub 2021 Apr 6.

Department of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.

Background: Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.

Methods: To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures.

Results: T-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs.

Conclusions: scRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner.
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http://dx.doi.org/10.1186/s12931-021-01675-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022543PMC
April 2021

Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge.

Arch Bronconeumol 2021 Apr 24;57 Suppl 2:59-61. Epub 2021 Feb 24.

Respiratory Institute, Hospital Clinic, University of Barcelona, C/Villaroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Roselló 149, 08036 Barcelona, Spain.

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http://dx.doi.org/10.1016/j.arbres.2021.01.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903150PMC
April 2021

Transitioning from infancy to adulthood: a black box full of opportunities.

Eur Respir J 2021 03 4;57(3). Epub 2021 Mar 4.

Institut d'Investigacions BIomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.

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http://dx.doi.org/10.1183/13993003.03997-2020DOI Listing
March 2021

Liver epigenome changes in patients with hepatopulmonary syndrome: A pilot study.

PLoS One 2021 25;16(2):e0245046. Epub 2021 Feb 25.

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.

The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245046PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906328PMC
July 2021

Low birth weight as a potential risk factor for severe COVID-19 in adults.

Sci Rep 2021 02 3;11(1):2909. Epub 2021 Feb 3.

BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), IDIBAPS, Centre for Biomedical Research on Rare Diseases (CIBER-ER), Universitat de Barcelona, Sabino de Arana 1, 08028, Barcelona, Spain.

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70 years) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤ 2.500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P = 0.012), male sex (aOR 3.39 [1.72-6.67], P < 0.001), hypertension (aOR 3.37 [1.69-6.72], P = 0.001), and LBW (aOR 3.61 [1.55-8.43], P = 0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.
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http://dx.doi.org/10.1038/s41598-021-82389-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859212PMC
February 2021

Phenotypic characterisation of early COPD: a prospective case-control study.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

CIBER de Enfermedades Respiratorias, Madrid, Spain.

The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case-control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) <0.7) and 197 controls. Results were contrasted with participants with similar inclusion criteria recruited into the ECLIPSE and COPDGene cohorts. Cases had moderate airflow limitation (FEV 71.3±20.8%) but were often symptomatic, used healthcare resources frequently, had air trapping (residual volume 150.6±55.5% ref.), had reduced diffusing capacity (84.2±20.7% ref.) and had frequent evidence of computed tomography (CT) emphysema (61%). Of note, less than half of cases (46%) had been previously diagnosed with COPD. Interestingly, they also often reported a family history of respiratory diseases and had been hospitalised because of respiratory problems before the age of 5 years more frequently than controls (12% 3%, p=0.009). By and large, these observations were reproduced when available in the ECLIPSE and COPDGene cohorts. These results show that early COPD is associated with substantial health impact and significant structural and functional abnormalities, albeit it is often not diagnosed (hence, treated). The fact that a sizeable proportion of patients with early COPD report a family history of respiratory diseases and/or early-life events (including hospitalisations before the age of 5 years) renders further support to the possibility of early-life origin of COPD.
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http://dx.doi.org/10.1183/23120541.00047-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533304PMC
October 2020

COPD 2020: changes and challenges.

Am J Physiol Lung Cell Mol Physiol 2020 11 23;319(5):L879-L883. Epub 2020 Sep 23.

CIBER Enfermedades Respiratorias, Barcelona, Spain.

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http://dx.doi.org/10.1152/ajplung.00429.2020DOI Listing
November 2020

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

ERJ Open Res 2020 Jul 14;6(3). Epub 2020 Sep 14.

University Department of Medicine, Cantonal Hospital Basell and Liestal, Basell, Switzerland.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.
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http://dx.doi.org/10.1183/23120541.00193-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487360PMC
July 2020

Chronic Obstructive Pulmonary Disease Pathogenesis.

Clin Chest Med 2020 09;41(3):307-314

Institut d'Investigacio August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red (CIBER) Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain.

Chronic obstructive pulmonary disease (COPD) has been traditionally considered a self-inflicted disease caused by tobacco smoking. Current available evidence, however, indicates that the pathogenesis of COPD needs to consider the dynamic and cumulative nature of a series of environment (including smoking plus other exposures)-host interactions that eventually determine lung development, maintenance, repair, and aging. By doing so, these factors modulate the trajectory of lung function of the individual through life and the odds of developing COPD through different routes, which likely represent different forms of the disease that require different preventive and therapeutic strategies.
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http://dx.doi.org/10.1016/j.ccm.2020.05.001DOI Listing
September 2020

Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?

Lancet Respir Med 2020 05 3;8(5):436-438. Epub 2020 Apr 3.

Respiratory Institute, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, University of Barcelona and National Spanish Network for Respiratory Research, Barcelona, Spain.

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http://dx.doi.org/10.1016/S2213-2600(20)30167-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270536PMC
May 2020

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity.

Respir Res 2020 Jan 13;21(1):21. Epub 2020 Jan 13.

Respiratory Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Autonomous University of Barcelona, Barcelona, Spain.

Background: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection.

Methods: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥10 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV), GOLD grade and level of symptoms (CAT questionnaire).

Results: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV, negatively with the CAT score, and lowest in GOLD grade D patients.

Conclusions: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.
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http://dx.doi.org/10.1186/s12931-020-1278-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958639PMC
January 2020

Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis.

Am J Respir Crit Care Med 2020 05;201(9):1078-1085

Centro de Investigación Biomedica en Red (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.

Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia. To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD. This was a long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis. Mean age was 70.3 years, 90.5% of patients were male, mean FEV was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/μl. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/μl (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/μl and CBI (HR, 2.925). Less than 100 circulating eosinophils/μl combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.
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http://dx.doi.org/10.1164/rccm.201908-1550OCDOI Listing
May 2020

Smoking and Interstitial lung damage/effects: A Plausible Association?

Arch Bronconeumol (Engl Ed) 2020 Jul 18;56(7):422-423. Epub 2019 Nov 18.

Servei de Pneumologia, Respiratory Institute, Hospital Clínic, Universitat de Barcelona, Barcelona, España; Centro de Investigación Biomedica en Red-Enfermedades Respiratorias (CIBERES); Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2019.09.006DOI Listing
July 2020

When Harry Met Sally, or When Machine Learning Met Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2020 02;201(3):263-265

Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)Barcelona, Spainand.

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http://dx.doi.org/10.1164/rccm.201911-2123EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999092PMC
February 2020

Multi-level immune response network in mild-moderate Chronic Obstructive Pulmonary Disease (COPD).

Respir Res 2019 Jul 12;20(1):152. Epub 2019 Jul 12.

CIBER Enfermedades Respiratorias, Barcelona, Spain.

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do immune cells relate within and between these two biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs. presence of disease is unclear.

Methods: To investigate these questions, we simultaneously collected lung tissue and blood from 65 individuals stratified by smoking habit and presence of the disease. The immune cell composition of both tissues was assessed by flow cytometry, whole lung transcriptome was determined with Affymetrix arrays, and we used Weighted Gene Co-expression Network Analysis (WGCNA) to integrate results.

Results: Main results showed that: (1) current smoking and the presence of COPD were both independently associated with a reduction in the proportion of lung T cells and an increase of macrophages, specifically those expressing CD80 + CD163+; (2) changes in the proportion of infiltrating macrophages, smoking status or the level of airflow limitation were associated to different WGCNA modules, which were enriched in iron ion transport, extracellular matrix and cilium organization gene ontologies; and, (3) circulating white blood cells counts were correlated with lung macrophages and T cells.

Conclusions: Mild-moderated COPD lung immune infiltrate is associated with the active smoking status and presence of disease; is associated with changes in whole lung tissue transcriptome and marginally reflected in blood.
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http://dx.doi.org/10.1186/s12931-019-1105-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626346PMC
July 2019

Relationship between the respiratory microbiome and the severity of airflow limitation, history of exacerbations and circulating eosinophils in COPD patients.

BMC Pulm Med 2019 Jun 24;19(1):112. Epub 2019 Jun 24.

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

Background: The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.

Methods: Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing. The microbiome composition was analysed with QIIME.

Results: We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera.

Conclusion: The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.
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http://dx.doi.org/10.1186/s12890-019-0867-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591812PMC
June 2019

Global lung health: the dangers of mild lung function impairment.

Lancet Glob Health 2019 05;7(5):e542-e543

Centro Investigación Biomédica En Red Enfermedades Respiratorias (CIBERES), Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain; Pulmonary Service, Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1016/S2214-109X(19)30156-1DOI Listing
May 2019

Smoking Impairs the Immunomodulatory Capacity of Lung-Resident Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease.

Am J Respir Cell Mol Biol 2019 11;61(5):575-583

Centro Investigación Biomédica en Red Enfermedades Respiratorias, Barcelona, Spain.

Tobacco smoking is the main environmental risk factor for chronic obstructive pulmonary disease (COPD), but not all smokers develop the disease. A population of lung-resident mesenchymal stem cells (LR-MSCs) exist in healthy lungs, but how tobacco smoking affects them and their role in COPD have not been assessed yet. Using a sphere-based culture technique, we isolated LR-MSCs from lung tissue obtained from nonsmokers and current and former smokers with and without COPD ( = 53). The cells were characterized by flow cytometry and Affymetrix arrays. Their immunomodulatory capacity was assessed using cocultures with T cells and after preincubation with 2.5% and 5% cigarette smoke extract. We were able to isolate LR-MSCs expressing similar phenotypic markers in all of the study groups. LR-MSCs from current smokers with COPD expressed different levels of CX3CL1 and CCL5 cytokines, and were unable to modulate CD8 T-cell proliferation. Preincubation of LR-MSCs with cigarette smoke extract reduced their immunomodulatory capacity. In conclusion, ) LR-MSCs can be isolated in similar amounts from never-smokers and smokers with and without COPD; ) their immunomodulatory capacity is impaired in current smokers with COPD, but not in those with normal lung function; and ) this is reversible after smoking cessation and is reproducible .
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http://dx.doi.org/10.1165/rcmb.2018-0351OCDOI Listing
November 2019

Lung function trajectories in health and disease.

Lancet Respir Med 2019 04 11;7(4):358-364. Epub 2019 Feb 11.

August Pi i Sunyer Biomedical Research Institute (IDIBAPS) Barcelona, Spain; Centro de Investigación Biomédica en Red, Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBER), Madrid, Spain.

The normal lung function trajectory from birth to death has three phases: a growth phase (from birth to early adulthood), a plateau phase (that lasts for a few years), and a decline phase resulting from physiological lung ageing. Numerous genetic and environmental factors can alter one or more of these phases. Evidence shows that several lung function trajectories exist throughout the life course and, importantly, that some of them are associated with substantial implications for health and disease. Here, we review the evidence, formulate a series of questions, and identify various challenges that need to be addressed to identify potential opportunities to promote respiratory health.
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http://dx.doi.org/10.1016/S2213-2600(18)30529-0DOI Listing
April 2019
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